Perfluoroalkyl-Modified Nucleic Acids for Direct Cell Entry
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Solution Overview
Problem
Nucleic acid drugs face challenges with poor cell membrane permeability, particularly siRNA, necessitating carriers like lipid nanoparticles or cationic polymer nanoparticles, which have inefficiencies and toxicity concerns, while polyfluoro compounds offer potential improvements but are not effectively integrated into nucleic acids for enhanced permeability.
Innovation Solution
Introducing a perfluoroalkyl group with 1 to 10 carbon atoms and optional ether-bonded oxygen atoms into nucleic acids to enhance cell membrane permeability, allowing direct cell introduction without additional transfection reagents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nucleic acid drugs are used for intracellular delivery, then high specificity and low side effects are achieved, but cell membrane permeability is poor
Solution Approach 1:
The patent modifies the chemical structure of nucleic acid drugs by introducing perfluoroalkyl groups with specific carbon chain lengths (1-10 atoms). This parameter change in molecular structure fundamentally alters the drug's interaction with cell membranes, enabling passive diffusion while preserving the nucleic acid's target-specific binding properties.
Solution Approach 2:
The invention creates a composite molecular structure combining traditional nucleic acid backbones with perfluoroalkyl side chains. This composite approach integrates the high specificity of nucleic acids with the membrane-permeable properties of perfluorinated compounds, achieving both target precision and cellular entry capability.
2Reliability
If siRNA is used for gene silencing, then high target specificity is achieved, but cell membrane permeability is inferior due to double-stranded structure and higher molecular weight
Solution Approach 1:
The patent applies perfluoroalkyl modifications to siRNA molecules, changing their physical-chemical parameters such as hydrophobicity and membrane affinity. This enables the double-stranded siRNA to traverse cell membranes via passive diffusion despite its inherent structural barriers, while maintaining its RNA interference function.
Solution Approach 2:
The perfluoroalkyl groups act as intermediary elements that facilitate the interaction between the hydrophilic nucleic acid and the hydrophobic cell membrane. These groups serve as a chemical bridge, enabling the siRNA to cross the membrane barrier without requiring external carriers.
3Object-affected harmful factors
If lipid nanoparticles or cationic polymer nanoparticles are used as carriers, then cell membrane permeability is improved, but transfection efficiency and toxicity remain problematic
Solution Approach 1:
The patent extracts and eliminates the need for external carrier systems by directly incorporating membrane-permeable perfluoroalkyl groups into the nucleic acid structure. This removes the intermediary carrier step entirely, avoiding the efficiency and toxicity issues associated with lipid or polymer nanoparticles.
Solution Approach 2:
The modified nucleic acid drugs become self-sufficient for cellular entry, utilizing their own integrated perfluoroalkyl groups to mediate membrane crossing. This self-service capability eliminates dependence on external transfection reagents, improving both efficiency and safety profiles.
4Object-affected harmful factors
If polyfluoro structures are incorporated into oligonucleotides, then cell membrane permeability is enhanced, but synthesis complexity increases
Solution Approach 1:
The patent divides the perfluoroalkyl modification into discrete, modular units that can be independently synthesized and then attached to the nucleic acid backbone during standard oligonucleotide synthesis. This segmentation approach simplifies the overall manufacturing process compared to attempting to synthesize fully modified nucleic acids in one step.
Data Source
AI summary
The present invention provides a nucleic acid for transfection in which a nucleic acid targeted for introduction into a cell and a cell membrane-permeable group are linked together, the cell membrane-permeable group contains a perfluoroalkyl group having 2 to 10 carbons, and the perfluoroalkyl group may have one to five ether-bonded oxygen atoms between the carbon atoms, and also provides a nucleic acid transfection method that involves bringing the nucleic acid for transfection into contact with a cell to introduce the nucleic acid into the cell.